Sarcoidosis Care Starts With Inflammation vs Fibrosis: Rohit Gupta, MD

Fibrosis and pulmonary hypertension remain the strongest markers of poor outcomes in pulmonary sarcoidosis, but current data do not yet support routine antifibrotic therapy in fibrotic disease, according to Rohit Gupta, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University and director of the sarcoidosis program at Temple University Hospital.

Gupta spoke with HCPLive after a sarcoidosis management session at the CHEST 2026 Annual Meeting, held October 18-21, 2026, in Phoenix, Arizona. He said advanced pulmonary sarcoidosis, marked by extensive fibrosis, sarcoidosis-associated pulmonary hypertension (SAPH), respiratory failure, or oxygen need, carries higher morbidity and mortality. Prognostic tools such as the Walsh and modified Walsh models combine pulmonary function and CT findings to identify patients at risk of poor outcomes.1

"We really do not know the trajectory of these patients who have fibrotic pulmonary sarcoidosis. Some of them are very stable and they do not die because of the fibrotic disease, but some would, and we do not know who are those patients at this time," Gupta said.

Progressive pulmonary fibrosis trials enrolled few patients with sarcoidosis, Gupta said, and some patients with fibrotic disease still have active inflammation which may respond to anti-inflammatory therapy with gains in forced vital capacity (FVC). He said antifibrotics may suit select patients with progression and no inflammatory activity, decided case by case.

Assessing disease activity remains difficult, Gupta said, noting serum angiotensin-converting enzyme has poor sensitivity and specificity, while soluble IL-2 receptor, C-reactive protein, and CT findings such as ground-glass opacities can help, with PET-CT used less often. For SAPH, he noted only 2 double-blind, placebo-controlled trials exist and called for dedicated multicenter trials, though carefully selected patients with precapillary disease can improve with treatment.

The session also covered the PREDMETH trial, in which methotrexate was noninferior to prednisone for change in percent-predicted FVC at 24 weeks as first-line therapy in 138 treatment-naive patients with pulmonary sarcoidosis (adjusted difference, −1.17 percentage points; 95% CI, −4.27 to 1.93).2 Gupta said methotrexate takes longer to improve symptoms and FVC but could serve as a first-line option, in line with efforts to limit cumulative steroid exposure.

References

1. Walsh SLF, Wells AU, Sverzellati N, et al. An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study. Lancet Respir Med. 2014;2(2):123-130.

2. Kahlmann V, Janssen Bonás M, Moor CC, et al. First-line treatment of pulmonary sarcoidosis with prednisone or methotrexate. N Engl J Med. 2025;393(3):231-242. doi:10.1056/NEJMoa2501443